Abstract

Background

Systematic analyses of loss-of-function phenotypes have been carried out for most
genes in Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster. Although such studies vastly expand our knowledge of single gene function, they
do not address redundancy in genetic networks. Developing tools for the systematic
mapping of genetic interactions is thus a key step in exploring the relationship between
genotype and phenotype.

Results

We established conditions for RNA interference (RNAi) in C. elegans to target multiple genes simultaneously in a high-throughput setting. Using this approach,
we can detect the great majority of previously known synthetic genetic interactions.
We used this assay to examine the redundancy of duplicated genes in the genome of
C. elegans that correspond to single orthologs in S. cerevisiae or D. melanogaster and identified 16 pairs of duplicated genes that have redundant functions. Remarkably,
14 of these redundant gene pairs were duplicated before the divergence of C. elegans and C. briggsae 80-110 million years ago, suggesting that there has been selective pressure to maintain
the overlap in function between some gene duplicates.

Conclusion

We established a high throughput method for examining genetic interactions using combinatorial
RNAi in C. elegans. Using this technique, we demonstrated that many duplicated genes can retain redundant
functions for more than 80 million years of evolution. This provides strong support
for evolutionary models that predict that genetic redundancy between duplicated genes
can be actively maintained by natural selection and is not just a transient side effect
of recent gene duplication events.